Shifts in Clinical Practice-Changing Acute Ischemic Stroke Research Over the Past Decade

The past decade has witnessed rapid growth of clinical trial programs in Europe and Asia, with randomized clinical trials (RCTs) publications from these regions outpacing those of the United States. However, limited data exist quantifying their relative influence on practice-defining results. Here, we evaluate these shifts by analyzing the geographic origin, funding source, and clinical impact of practice-changing RCTs.

From the 2018 and 2026 American Heart Association/American Stroke Association Acute Ischemic Stroke guidelines, we identified RCTs supporting new recommendations and extracted geographic origin (China/Europe/United States/Other), funding source (government/academic/nonprofit versus industry (private/mixed); National Institutes of Health versus non-National Institutes of Health), and research topic (endovascular therapy, thrombolysis, imaging, poststroke care, and prehospital and systems of care). Analyses used unweighted, reference-density-weighted, and clinical-impact-weighted strategies. Temporal trends were assessed using the χ²/Fisher exact tests, with the Rao-Scott adjusted χ² tests accounting for weighting.

We identified 21 new recommendations (47 RCTs) in 2018 and 45 (89 RCTs) in 2026. In 2018, Europe led (51.1%), followed by the United States (31.9%), while China and other regions contributed minimally. By 2026, Europe remained first (36%), China rose to second (29.2%), and the United States declined to the smallest share (14.6%), across all weighted analyses (P<0.01). National Institutes of Health-funded trials declined significantly from 21.3% (unweighted), 27.4% (reference-density-weighted), and 27.3% (clinical-impact-weighted) in 2018 to 4.5%, 4.8%, and 3.5% respectively in 2026 (P<0.01 across all weighted strategies).

In this analysis, we identify a shift in practice-guiding research away from United States-based clinical trials and increasingly towards Europe and China. United States-based RCTs fell from the second most cited to the least cited sources of recommendations. National Institutes of Health-funded RCTs fell from nearly one-quarter of guideline-cited RCTs in 2018 to <5% in 2026, highlighting increasing reliance on non-US studies to inform US clinical care.